Gene expression
Gene expression
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DOI：
10.1182/blood.v89.11.3925
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发表时间：
1997-06-01
期刊：
影响因子：
20.3
通讯作者：
Andrews, NC
中科院分区：
文献类型：
--
作者：
Blank, V;Kim, MJ;Andrews, NC
哺乳动物珠蛋白基因表达通过AP-1超家族碱性亮氨酸拉链蛋白识别的NF-E2元件激活。NF-EP DNA结合的特异性由邻近核心AP-1基序的几个核苷酸决定，核心AP-1基序包含Maf亚家族转录因子的识别位点。早期的工作提出，p18（MafK）与造血特异性蛋白p45 NF-E2形成异源二聚体，通过NF-EP位点激活转录。然而，没有直接证据表明p18（MafK）在体内发挥这种功能;事实上，缺乏p18（MafK）的小鼠没有表型。在这里，我们描述了一个新的cDNA克隆，编码人同源的鸡MafG，人MafG与p45 NF-E2异源二聚化，并结合DNA的特异性相同的纯化的NF-EP DNA结合活性。p45和MafG的栓系异源二聚体在支持α-和β-珠蛋白的表达以及促进CB 3（p45缺陷型小鼠红白血病细胞系）中的红系分化中具有完全功能。这些结果表明，人MafG可以作为p45 NF-E2的功能伴侣，并表明p45/MafG异源二聚体在红细胞生成的调节中起作用。(C)1997年，美国血液学会。
Mammalian globin gene expression is activated through NF-E2 elements recognized by basic-leucine zipper proteins of the AP-1 superfamily. The specificity of NF-EP DNA binding is determined by several nucleotides adjacent to a core AP-1 motif, comprising a recognition site for transcription factors of the Maf subfamily. Earlier work proposed that p18(MafK) forms a heterodimer with hematopoietic-specific protein p45 NF-E2 to activate transcription through NF-EP sites. However, there was no direct evidence that p18(MafK) serves this function in vivo; in fact, mice lacking p18(MafK) have no phenotype. Here we describe a novel cDNA clone that encodes the human homolog of chicken MafG, Human MafG heterodimerizes with p45 NF-E2 and binds DNA with specificity identical to that of purified NF-EP DNA binding activity. A tethered heterodimer of p45 and MafG is fully functional in supporting expression of alpha- and beta-globin, and in promoting erythroid differentiation in CB3, a p45-deficient mouse erythroleukemia cell line. These results indicate that human MafG can serve as a functional partner for p45 NF-E2, and suggest that the p45/MafG heterodimer plays a role in the regulation of erythropoiesis. (C) 1997 by The American Society of Hematology.